The availability of 17 large Utah kindreds with herditary hemochromatosis provides an opportunity 1) to establish the mode of inheritance of the disease, 2) to describe the phenotypic expression of the disease in heterozygotes and homozygotes, 3) to establish appropriate diagnostic criteria of the disease, 4) to define the relationship of the hemochromatosis gene to "secondary" non-transfusional hemochromatosis such as occurs in a few patients with hemolytic anemia, sideroblastic anemia, porphyria cutanea tarda and B Thalassemia minor, and 5) to study the metabolic defect and identify the deficient or aberrant gene product. We have now studied 420 individuals in 17 pedigrees. The disease is inherited in an autosomal recessive fashion with only partial expression in women. The gene maps in close proximity to the HLA-A locus on chromosome six. We estimate to gene frequency in the Utah population of 5.6 percent. This calculates to a disease frequency of 0.3 percent and a heterozygote frequency of 10.6 percent.